KLF6 mediated mechanism as a therapeutic target in aortic diseases

以往的研究表明，kruppel样因子（KLFs）在心血管系统中起着重要作用。初步研究表明，KLF6在心血管发育和重构（如心脏纤维化）中发挥作用。在这项研究中，我们接下来的目标是破译KLF6介导主动脉病变（如主动脉瘤或夹层）的机制。持续输注血管紧张素II （AngII）可降低klf6+/-小鼠主动脉壁和血清中tgfβ -1表达水平，降低血压升高（野生型150 ~ 160 mmHg， klf6+/- 100 ~ 120 mmHg），提示可能通过抑制klf6控制血压。另一方面，KLF6+/小鼠在AngII + Cacl2形成主动脉瘤/夹层时表现出加速的主动脉重构，如炎症细胞浸润或MMP-2诱导和主动脉壁破坏。这些数据共同显示了主动脉病变的双期机制，表明精心决定KLF6靶向治疗的重要性。

Previous studies suggest that Kruppel-like factors (KLFs) play important roles in the cardiovasculature. Preliminary studies indicated that KLF6 have roles in cardiovascular development and remodeling such as cardiac fibrosis. In this study, we next aimed to decipher the mechanism in which KLF6 mediates aortic pathologies such as aortic aneurysm or dissection. Continuous angiotensin II (AngII) infusion in klf6+/- mice resulted in decreased TGFbeta-1 expression levels both in aortic wall and serum in KLF6+/- mice, and diminished blood pressure increase (wild-type 150-160 mmHg, KLF6+/- 100-120 mmHg), which indicates possibility of blood pressure control gy KLF6 inhibition. On the other hand, KLF6+/ mice showed accelerated aortic remodeling such as inflammatory cell infiltration or MMP-2 induction and aortic walldestruction in aortic aneurysm/dissection formation with AngII + Cacl2. These data collectively showed the biphasic mechanism in aortic pathologies, indicating the importanc of meticulous decision of KLF6 targeting therapies.